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1.
Article En | MEDLINE | ID: mdl-38326979

BACKGROUND AND AIM: The study aims to evaluate the feasibility of body mass index (BMI)-based individualized small bowel preparation for computed tomography enterography (CTE). METHODS: In this prospective randomized controlled study, patients undergoing CTE were randomly assigned to the individualized group or standardized group. Those in individualized group were given different volumes of mannitol solution based on BMI (1000 mL for patients with BMI < 18.5 kg/m2 , 1500 mL for patients with 18.5 kg/m2  ≤ BMI < 25 kg/m2 and 2000 mL for patients with BMI ≥ 25 kg/m2 ) while patients in the standardized group were all asked to consume 1500-mL mannitol solution. CTE images were reviewed by two experienced radiologists blindly. Each segment of the small bowel was assessed for small bowel image quality and disease detection rates. Patients were invited to record a diary regarding adverse events and acceptance. RESULTS: A total of 203 patients were enrolled and randomly divided into two groups. For patients with BMI < 18.5 kg/m2 , 1000-mL mannitol solution permitted a significantly lower rate of flatulence (P = 0.045) and defecating frequency (P = 0.011) as well as higher acceptance score (P = 0.015), but did not affect bowel image quality and diseases detection compared with conventional dosage. For patients with BMI ≥ 25 kg/m2 , 2000-mL mannitol solution provided better overall image quality (P = 0.033) but comparable rates of adverse events and patients' acceptance compared with conventional dosage. CONCLUSIONS: Individualized bowel preparation could achieve both satisfactory image quality and patients' acceptance thus might be an acceptable alternative in CTE.

2.
Inflamm Bowel Dis ; 30(1): 114-124, 2024 Jan 05.
Article En | MEDLINE | ID: mdl-37454276

BACKGROUND: Mucosal healing is one of the principal therapeutic targets for ulcerative colitis (UC). Mitochondria are dynamic organelles that undergo constant fusion and fission; however, the process that is most conducive to mucosal healing remains unclear. This study investigated the role of mitochondrial fission in mucosal healing in UC patients. METHODS: Quantitative polymerase chain reaction, Western blotting, and immunostaining were used to detect mitochondrial fission in UC patients and a dextran sulfate sodium-induced colitis model. Colonic organoids were used to investigate the role of mitochondrial fission in butyrate metabolism. Enzyme activity assays were performed to identify the key proteins involved in this mechanism. RESULTS: It was found that inhibition of mitochondrial fission promoted mucosal healing in mice and that there was an increase in mitochondrial fission in colonic epithelial cells of UC patients. Excessive fission inhibits stem cell proliferation by impairing butyrate metabolism in colonic organoids. The mitochondrial fission antagonist P110 failed to promote mucosal healing in antibiotic-treated mice, and the addition of exogenous butyrate reversed this effect. Increased butyrate exposure in the colonic stem cell niche has also been observed in UC patients. Mechanistically, enzyme activity assays on colonic organoids revealed that excessive fission inhibits mitochondrial acetoacetyl-CoA thiolase activity via reactive oxygen species. CONCLUSIONS: Collectively, these data indicate that excessive mitochondrial fission suppresses mucosal repair by inhibiting butyrate metabolism and provides a potential target for mucosal healing in patients with ulcerative colitis.


Colitis, Ulcerative , Humans , Animals , Mice , Colitis, Ulcerative/drug therapy , Mitochondrial Dynamics , Intestinal Mucosa/metabolism , Butyrates/pharmacology , Butyrates/metabolism
3.
Medicine (Baltimore) ; 102(43): e35781, 2023 Oct 27.
Article En | MEDLINE | ID: mdl-37904420

RATIONALE: Among numerous types of nontuberculous mycobacterial infections, Mycobacterium avium complex is a related group of species, which can cause various diseases in humans. Mycobacterium marseillense is a member of the Mycobacterium avium complex, which accounts for only a small proportion of species, but causes rare diseases affecting the lungs, lymph nodes, skin, and tendon sheath. So far, very few cases have been reported. PATIENT CONCERNS: A 76-year-old male of peculiar skin infection. Metagenomic Next Generation Sequencing and bacterial culture of skin secretions revealed M marseillense. To the best of our knowledge, we report the first patient diagnosed with disseminated M marseillense infection. Here, we identified only 8 other reports of patients with M marseillense infection. DIAGNOSES: Disseminated M marseillense infection. INTERVENTIONS: The patient was treated with clarithromycin, rifampicin, moxifloxacin, and ethambutol. OUTCOMES: The skin lesions of the patient showed significant improvement, and his pruritus and limb pain were notably reduced after 7 months of follow-up. LESSONS: Metagenomic Next Generation Sequencing may be a useful tool to diagnose M marseillense infection, but the results should be confirmed by culture and mycobacterial identification.


Mycobacterium Infections, Nontuberculous , Mycobacterium , Male , Humans , Aged , Mycobacterium avium Complex , Mycobacterium Infections, Nontuberculous/diagnosis , Clarithromycin/therapeutic use
4.
J Gastroenterol Hepatol ; 38(6): 962-969, 2023 Jun.
Article En | MEDLINE | ID: mdl-37094943

BACKGROUND AND AIM: Lugol chromoendoscopy is the standard technique to detect an esophageal squamous cell carcinoma (ESCC). However, a high concentration of Lugol's solution can induce mucosal injury and adverse events. We aimed to investigate the optimal concentration of Lugol's solution to reduce mucosal injury and adverse events without degrading image quality. METHODS: This was a two-phase double-blind randomized controlled trial. In phase I, 200 eligible patients underwent esophagogastroduodenoscopy and then were randomly (1:1:1:1:1) sprayed with 1.2%, 1.0%, 0.8%, 0.6%, or 0.4% Lugol's solution. Image quality, gastric mucosal injury, adverse events, and operation satisfaction were compared to investigate the minimal effective concentration. In phase II, 42 cases of endoscopic mucosectomy for early ESCC were included. The patients were randomly assigned (1:1) to the minimal effective (0.6%) or conventional (1.2%) concentration of Lugol's solution for further comparison of the effectiveness. RESULTS: In phase I, the gastric mucosal injury was significantly reduced in 0.6% group (P < 0.05). Furthermore, there was no statistical significance in image quality between 0.6% and higher concentrations of Lugol's solution (P > 0.05, respectively). It also showed that the operation satisfaction decreased in 1.2% group compared with the lower concentration groups (P < 0.05). In phase II, the complete resection rate was 100% in both groups, while 0.6% Lugol's solution showed higher operation satisfaction (W = 554.500, P = 0.005). CONCLUSIONS: The study indicates that 0.6% might be the optimal concentration of Lugol's solution for early detection and delineation of ESCC, considering minimal mucosal injury and satisfied image. The registry of clinical trials: ClinicalTrials.gov (NCT03180944).


Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Neoplasms/pathology , Esophagoscopy/methods , Coloring Agents
5.
Helicobacter ; 27(2): e12880, 2022 Apr.
Article En | MEDLINE | ID: mdl-35150600

BACKGROUND: Helicobacter pylori (H. pylori) infections are of serious concern due to the associated risk of gastric cancer. However, many patients have poor medication and therapy compliance, which makes it difficult to eradicate their infections. This points to the need for stronger educational interventions aimed at enhancing compliance, thus increasing the potential for treatment success. As such, this study conducted a meta-analysis to clarify the effects of enhanced patient education (EPE) programs for H. pylori. MATERIALS AND METHODS: We searched electronic databases (PubMed, EMBASE, Web of Science, and Cochrane Library) for randomized controlled trials (RCTs) on health education for patients infected with H. pylori from inception to June 2021. The primary outcome was the eradication rate of H. pylori, while the secondary outcomes included the incidence of individual adverse symptoms, treatment compliance, clinical symptom remission after treatment, and patient satisfaction. We used the fixed or random-effects model to pool the risk ratio (RR), with 95% confidence interval. We also conducted sensitivity and subgroup analyses. RESULTS: Our search returned seven relevant studies across a total of 1,433 patients. Compared with controls, EPE was significantly associated with improved H. pylori eradication rates (RR = 1.16, 95%CI: 1.04-1.29, p = 0.006) and patient compliance (RR = 1.48, 95%CI: 1.14-1.93, p = 0.003). A subgroup analysis also showed that EPE benefits were consistent across patients with different eradication programs, WeChat intervention plans, and intervention frequencies (p < 0.05). However, there were no significant differences in the total adverse effects, common side effects (diarrhea, nausea, abdominal pain, taste disorder, and skin rash), or discontinuation rate (p > 0.05). CONCLUSIONS: Patient education is inexpensive, safe, and convenient. In this context, our findings suggest that enhanced educational interventions have positive effects on both the H. pylori eradication rate and adherence among infected patients, and thus constitute promising complements to clinical treatment regimens.


Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Anti-Bacterial Agents/pharmacology , Drug Therapy, Combination , Helicobacter Infections/diagnosis , Humans , Stomach Neoplasms/drug therapy
7.
Dig Endosc ; 33(7): 1075-1084, 2021 Nov.
Article En | MEDLINE | ID: mdl-33275789

BACKGROUND AND AIMS: Endoscopic diagnosis of early esophageal squamous cell cancer (ESCC) is complicated and dependent on operators' experience. This study aimed to develop an artificial intelligence (AI) model for automatic diagnosis of early ESCC. METHODS: Non-magnifying and magnifying endoscopic images of normal/noncancerous lesions, early ESCC, and advanced esophageal cancer (AEC) were retrospectively obtained from Qilu Hospital of Shandong University. A total of 10,988 images from 5075 cases were chosen for training and validation. Another 2309 images from 1055 cases were collected for testing. One hundred and four real-time videos were also collected to evaluate the diagnostic performance of the AI model. The diagnostic performance of the AI model was compared with endoscopists by magnifying images and the assistant efficiency of the AI model for novices was evaluated. RESULTS: The AI diagnosis for non-magnifying images showed a per-patient accuracy, sensitivity, and specificity of 99.5%, 100%, 99.5% for white light imaging, and 97.0%, 97.2%, 96.4% for optical enhancement/iodine straining images. Regarding diagnosis for magnifying images, the per-patient accuracy, sensitivity, and specificity were 88.1%, 90.9%, and 85.0%. The diagnostic accuracy of the AI model was similar to experts (84.5%, P = 0.205) and superior to novices (68.5%, P = 0.005). The diagnostic performance of novices was significantly improved by AI assistance. When it comes to the diagnosis for real-time videos, the AI model showed acceptable performance as well. CONCLUSIONS: The AI model could accurately recognize early ESCC among noncancerous mucosa and AEC. It could be a potential assistant for endoscopists, especially for novices.


Carcinoma, Squamous Cell , Esophageal Neoplasms , Artificial Intelligence , Carcinoma, Squamous Cell/diagnostic imaging , Esophageal Neoplasms/diagnostic imaging , Humans , Narrow Band Imaging , Retrospective Studies
8.
BMJ Open ; 10(10): e037375, 2020 10 19.
Article En | MEDLINE | ID: mdl-33077561

OBJECTIVES: Furazolidone containing regimen is effectivefor Helicobacter pylori (H. pylori) infection, but its safetyremains controversial. To assess the safety of furazolidone containing regimenin H. pylori infection. DESIGN: A systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Cochrane Library, Web of Science and Scopus databases were systematically searched for eligible randomised controlled trials. ELIGIBILITY CRITERIA: Studies comparing furazolidone with non-furazolidone-containing regimen, variable durations or doses of furazolidone were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently selected studies and extracted data. Primary outcomes were the risk of total adverse events (AEs), serious AEs and severe AEs, expressed as relative risk (RR) with 95% CI. Secondary outcomes contained the incidence of individual adverse symptoms, AE-related treatment discontinuation and compliance. RESULTS: Twenty-six articles were identified from 2039 searched records, of which 14 studies (n=2540) compared furazolidone with other antibiotics. The eradication rates of furazolidone-containing regimen were higher than those of other antibiotics in both intention-to-treat (RR 1.06, 95% CI 1.01 to 1.12) and per-protocol analysis (RR 1.05, 95% CI 1.00 to 1.10). Only two serious AEs were reported in furazolidone group (2/1221, 0.16%). No significant increased risk was observed for the incidence of total AEs (RR 1.04, 95% CI 0.89 to 1.21) and severe AEs (RR 1.81, 95% CI 0.91 to 3.60). Twelve studies (n=3139) compared different durations of furazolidone, and four studies (n=343) assessed variable doses. Elevated risk of total AEs and severe AEs were only found in a high daily dose of furazolidone rather than prolonged duration. The incidence of AE-related treatment discontinuation and compliance of patients were all similar, irrespective of dose and duration adjustments. CONCLUSION: Furazolidone-containing regimen has a similar risk of AEs and compliance as non-furazolidone-containing regimen. A low daily dose of 200 mg is well-tolerated for 14 day regimen and should be first considered. PROSPERO REGISTRATION NUMBER: CRD42019137247.


Helicobacter Infections , Helicobacter pylori , Anti-Bacterial Agents/adverse effects , Drug Therapy, Combination , Furazolidone/adverse effects , Helicobacter Infections/drug therapy , Humans
9.
J Dig Dis ; 21(10): 549-557, 2020 Oct.
Article En | MEDLINE | ID: mdl-32833285

OBJECTIVE: In this study we aimed to compare the efficacy and safety of two personalized rescue therapies for Helicobacter pylori infection. METHODS: An open-label, single-center, randomized controlled trial was conducted. Patients who had failed one or two regimens for H. pylori infection were randomized to receive a 14-day bismuth-containing quadruple therapy guided by antimicrobial susceptibility testing (AST) or personal medication history (PMH). In the AST group, either two of amoxicillin, clarithromycin, metronidazole or levofloxacin were prescribed according to the AST. In the PMH group, amoxicillin plus either levofloxacin or furazolidone were prescribed based on the patient's history of quinolone use. The primary outcomes were eradication rates confirmed by an urea breath test 6 weeks after treatment. The secondary outcomes were adherence, incidence of adverse events (AE) and cost-effectiveness. RESULTS: Altogether 164 with a positive culture received AST-guided therapy and 192 received PMH-guided therapy, respectively. Both AST- and PMH-guided therapies achieved comparable eradication rate (intention-to-treat analysis: 78.10% vs 74.29%, P = 0.42; per-protocol analysis: 87.10% vs 88.64%, P = 0.80). The AST clarithromycin regimen had a lower per-protocol eradication rate than the levofloxacin (75.47% vs 96.30%, P = 0.03) or furazolidone-containing regimen (75.47% vs 92.75%, P = 0.02). Both groups had high compliance with low incidences of AE, and PMH-guided therapy had a lower medical cost. CONCLUSIONS: AST-guided therapy was not superior to PMH-guided therapy as a second- or third-line treatment for H. pylori infection. Considering the cost-effectiveness, PMH therapy is clinically more favorable.


Anti-Bacterial Agents , Helicobacter Infections , Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Bismuth/therapeutic use , Clarithromycin/therapeutic use , Cost-Benefit Analysis , Drug Therapy, Combination , Furazolidone/therapeutic use , Helicobacter Infections/drug therapy , Helicobacter pylori , Humans , Levofloxacin/therapeutic use , Metronidazole/therapeutic use , Treatment Outcome
10.
J Gastroenterol Hepatol ; 35(12): 2066-2073, 2020 Dec.
Article En | MEDLINE | ID: mdl-32562282

BACKGROUND AND AIMS: Add-on devices have been widely used in clinical practice. The aim of this meta-analysis was to compare the adenoma detection rate between Endocuff-assisted colonoscopy (EAC) and cap-assisted colonoscopy (CAC). METHODS: PubMed, EMBASE, SCOPUS, and Cochrane databases were searched. Outcomes included adenoma detection rate, cecal intubation rate, cecal intubation time, and withdrawal time. Dichotomous data were pooled to obtain the odds ratio or risk ratio. Continuous data were pooled using the mean difference. RESULTS: Of the 240 articles reviewed, six randomized controlled trials were included, with a total of 1994 patients. In the meta-analysis, no statistical difference in adenoma detection rate was detected between EAC and CAC (47.0% vs 45.1%; P = 0.33). EAC significantly improved detection rate of diminutive adenomas/polyps compared with CAC (P = 0.01). Cecal intubation was achieved in 96.5% in EAC group and 97.9% in CAC group (P = 0.04). Besides, no statistical difference was found in cecal intubation time (P = 0.86), withdrawal time (P = 0.88), small adenomas/polyps (P = 0.60), or large adenomas/polyps (P = 0.95). CONCLUSION: EAC and CAC have their respective merits. EAC significantly improve the detection of diminutive adenomas/polyps. CAC was better in cecal intubation rate.


Adenoma/diagnosis , Colonic Neoplasms/diagnosis , Colonoscopy/methods , Randomized Controlled Trials as Topic , Adenoma/pathology , Colonic Neoplasms/pathology , Colonic Polyps/diagnosis , Colonic Polyps/pathology , Female , Humans , Male
11.
Clin Transl Gastroenterol ; 12(1): e00282, 2020 12 22.
Article En | MEDLINE | ID: mdl-33395075

INTRODUCTION: Conventional gastrointestinal (GI) endoscopy reports written by physicians are time consuming and might have obvious heterogeneity or omissions, impairing the efficiency and multicenter consultation potential. We aimed to develop and validate an image recognition-based structured report generation system (ISRGS) through a multicenter database and to assess its diagnostic performance. METHODS: First, we developed and evaluated an ISRGS combining real-time video capture, site identification, lesion detection, subcharacteristics analysis, and structured report generation. White light and chromoendoscopy images from patients with GI lesions were eligible for study inclusion. A total of 46,987 images from 9 tertiary hospitals were used to train, validate, and multicenter test (6:2:2). Moreover, 5,699 images were prospectively enrolled from Qilu Hospital of Shandong University to further assess the system in a prospective test set. The primary outcome was the diagnosis performance of GI lesions in multicenter and prospective tests. RESULTS: The overall accuracy in identifying early esophageal cancer, early gastric cancer, early colorectal cancer, esophageal varices, reflux esophagitis, Barrett's esophagus, chronic atrophic gastritis, gastric ulcer, colorectal polyp, and ulcerative colitis was 0.8841 (95% confidence interval, 0.8775-0.8904) and 0.8965 (0.8883-0.9041) in multicenter and prospective tests, respectively. The accuracy of cecum and upper GI site identification were 0.9978 (0.9969-0.9984) and 0.8513 (0.8399-0.8620), respectively. The accuracy of staining discrimination was 0.9489 (0.9396-0.9568). The relative error of size measurement was 4.04% (range 0.75%-7.39%). DISCUSSION: ISRGS is a reliable computer-aided endoscopic report generation system that might assist endoscopists working at various hospital levels to generate standardized and accurate endoscopy reports (http://links.lww.com/CTG/A485).


Endoscopy, Gastrointestinal/methods , Gastrointestinal Diseases/diagnosis , Gastrointestinal Tract/diagnostic imaging , Health Information Exchange , Image Interpretation, Computer-Assisted/methods , China , Databases as Topic , Gastrointestinal Diseases/pathology , Gastrointestinal Tract/pathology , Humans , Prospective Studies , Reproducibility of Results , Retrospective Studies , Video Recording
12.
J Dig Dis ; 20(11): 578-588, 2019 Nov.
Article En | MEDLINE | ID: mdl-31429214

OBJECTIVE: This meta-analysis aimed to evaluate whether EndoCuff-assisted colonoscopy (EAC) could improve adenoma detection rate (ADR) compared with standard colonoscopy (SC). METHODS: PubMed, EMBASE, Scopus, Cochrane Library, and Google Scholar databases were searched for articles published up to March 2019. All pure randomized controlled trials comparing ADR between EAC and SC groups were included. Dichotomous data were pooled to obtain the odds ratio with a 95% confidence interval (CI), whereas continuous data were pooled using a mean difference with 95% CI. Review Manager Version 5.3 was used for data analysis. RESULTS: Thirteen randomized controlled trials consisting of 9038 patients (EAC: 4574; SC: 4464) were included. The EAC group showed significant superiority over the SC group in ADR (odds ratio 1.37, 95% CI 1.15-1.62). However, there were no differences between the EAC and SC groups in adverse events, cecal intubation rate, and cecal intubation time. CONCLUSIONS: EAC could significantly improve ADR without increasing adverse events, especially for operators with low ADRs. In addition, no significant difference was observed in cecal intubation time and cecal intubation rate between EAC and SC.


Adenoma/diagnosis , Colonoscopy/methods , Colorectal Neoplasms/diagnosis , Colonoscopy/adverse effects , Humans , Intubation, Gastrointestinal , Randomized Controlled Trials as Topic , Time Factors
13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(2): 248-252, 2017 Mar.
Article Zh | MEDLINE | ID: mdl-28612536

OBJECTIVES: To determine the impact of long-term use of antibiotics and ultraviolet radiation on the resistance of Acinetobacter baumannii to tigecycline and the viability of tigecycline-resistant Acinetobacter baumannii . METHODS: Three strains of tigecycline sensitive Acinetobacter baumannii were selected. Tigecycline resistance was induced through multi-step method or by ultraviolet radiation. Two strains of tigecycline resistant Acinetobacter baumannii were repeatedly passaged on blank MHA plates, for the purpose of determination of minimum inhibitory concentrations (MICs) of tigecycline using broth microdilution method. The tigecycline sensitive (b38) and homologous resistant Acinetobacter baumannii (b38!d) were cultured separately and conjointly to evaluate its fitness costs of tigecycline resistance. RESULTS: Tigecycline resistant strains were successfully induced using multi-step method. Ultraviolet radiation did not change the sensitivity of the three strains to tigecycline, but elevated the MICs of tigecycline. The MICs of tigecycline did not change over 40 generations. It took much more time for the resistant strains to reach logarithmic growth phase and plateau phase compared with the tigecycline sensitive strains. With repeated passage, the tigecycline resistant strains decreased rapidly, even vanished in conjointly culture. CONCLUSION: Acinetobacter baumannii can acquire tigecycline resistance. The resistance may have genetic stability. The resistant strains have less adaptability than the sensitive strains.


Acinetobacter baumannii/drug effects , Acinetobacter baumannii/radiation effects , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Tigecycline/pharmacology , Ultraviolet Rays , Microbial Sensitivity Tests
14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 45(3): 437-41, 2014 May.
Article Zh | MEDLINE | ID: mdl-24941813

OBJECTIVE: To study the prevalence of 16S rRNA methylase genes in extended-spectrum-lactamascs (ESBLs)-producing Enterobacteriacea, and the correlations of 16S rRNA methylase genes with anminoglycoside resistnace. METHODS: Seventy-four ESBLs-producing Enterobacteriacea stains were isolated from urinary tract infections. Minimal inhibitory concentrations (MICs) of 5 aminoglycosides against the ESBLs-producing Enterobacteriacea were detected by two-fold agar dilution method. PCR amplification and DNA sequencing were used for screening and identifying 16S rRNA methylase genes. The clonality of 16S rRNA methylase gene positive ESBLs-producing Enterobacteriaceae was assessed by multilocus sequence typing (MLST). RESULTS: The bacterial resistant rates to gentamycin, netilmicin, tobramycin,amikacin and isepamicin were 93.4%, 18.4%, 13.2%, 5.3% and 5.3%, respectively. Tweenty-two out of 74 clinical isolates were 16S rRNA methylase genes positive (29.7%), including 18 armA gene and 7 rmtB gene, and 3 strains with both genes. The resistant rates of those 22 strains to gentamycin , netilmicin, tobramycin, amikacin and isepamicin were 100%, 100%, 59.1%, 18.2% and 18.2%, respectively. Among 19 E. coli isolates, seven sequence types (STs) were identified, named as ST117 (12 strains), ST2003 (2 strains), ST3843 (1 strain), ST915 (1 strain), ST844 (1 strain), ST2581 (1 strain) and ST2922 (1 strain). MLST showed that 3 K. pneumoniae isolates were nonclonal. CONCLUSION: 16S rRNA methylase genes were widely distributed in urinary ESBLs-producing Enterobacteriacea, showing obvious relationship with the resistance to aminoglycosides. The therapy of Amikacin or Isepamicin may be considered in UTIs with 16S rRNA gene positive ESBLs-producing Enterobacteriacea.


Enterobacteriaceae/genetics , Methyltransferases/genetics , Urinary Tract Infections/microbiology , Aminoglycosides/pharmacology , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Drug Resistance, Bacterial/genetics , Enterobacteriaceae/classification , Genotype , Humans , Microbial Sensitivity Tests , Multilocus Sequence Typing
15.
J Chin Med Assoc ; 68(2): 65-72, 2005 Feb.
Article En | MEDLINE | ID: mdl-15759817

BACKGROUND: This study was designed to compare the efficacy and safety of thymosin-alphal (T-alpha1) with that of interferon-alpha (IFN-alpha) in patients with chronic hepatitis B who were positive for hepatitis B virus (HBV) DNA and hepatitis B envelope antibody (anti-HBe). METHODS: Fifty-six patients were randomly divided into groups A and B. Both groups were comparable (p > 0.05) at baseline regarding age, sex, and alanine aminotransferase (ALT) levels. Group A patients received T-alpha1 1.6 mg subcutaneously twice weekly, while group B patients received IFN-alpha 5 million IU daily for 15 days, then thrice weekly for 6 months. Results from the 2 groups were compared with data from a group of 30 patients never treated with IFN-alpha and who were followed-up for 12 months (historical control [HC] group); the 3 groups were comparable (p > 0.05). RESULTS: After treatment, a complete response (ALT normalization and HBV DNA loss) occurred in 8 of 26 patients in group A (30.8%) and 14 of 30 in group B (46.7%; chi2 = 1.476, p = 0.224). After a follow-up period of 6 months, a complete response was observed in 11 of 26 patients in group A (42.3%) and 7 of 30 in group B (23.3%; chi2 = 2.299, p = 0.129). The rate of complete response was significantly greater in the IFN-alpha than HC group at the end of therapy (46.7% vs 3.3%; chi2 = 15.022, p = 0.0001), and in the T-alphal than HC group at the end of follow-up (42.3% vs 3.3%; chi2 = 12.566, p = 0.0001). Ten of the 12 T-alphal responders (i.e. partial responders; 83.3%) experienced sustained, non-detectable HBV DNA after 6 months' treatment; 6 of the 14 T-alphal non-responders (42.9%) showed a delayed response of non-detectable HBV DNA during the follow-up period. Corresponding values for group B patients were 50% (9/18) and 0% (0/12). The rate of delayed response was significantly higher in group A than the other 2 groups (chi2 = 6.686, p = 0.010; chi2 = 4.964, p = 0.038), whereas the rate of flare was higher in group B than in the other 2 groups (chi2 = 3.445, p = 0.063; chi2 = 7.668, p = 0.006), during the follow-up period. Unlike IFN-alpha, T-alphal was well tolerated, i.e. no adverse effects were noted in group A. CONCLUSION: These results suggest that a 6-month course of T-alpha1 therapy is effective and safe in patients with anti-HBe-positive chronic hepatitis B; T-alpha1 can reduce HBV replication in such patients. Compared with IFN-alpha, T-alpha1 is better tolerated and seems to induce a gradual and more sustained normalization of ALT and loss of HBV DNA. Combination therapy with T-alpha1 and IFN-alpha or nucleoside analogs for hepatitis B warrants further study.


Hepatitis B, Chronic/drug therapy , Interferon-alpha/therapeutic use , Thymosin/analogs & derivatives , Thymosin/therapeutic use , Adjuvants, Immunologic/therapeutic use , Adult , Alanine Transaminase/drug effects , Alanine Transaminase/metabolism , Antiviral Agents/therapeutic use , DNA, Viral/metabolism , Female , Hepatitis B Antigens/immunology , Hepatitis B Surface Antigens/immunology , Hepatitis B virus/drug effects , Hepatitis B virus/genetics , Hepatitis B virus/immunology , Humans , Male , Middle Aged , Thymalfasin , Treatment Outcome
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